My PhD project studies how the temporally sequential Hox gene expression is regulated during head-tail patterning of the frog embryo. This question has not been solved and remains one of the... Show moreMy PhD project studies how the temporally sequential Hox gene expression is regulated during head-tail patterning of the frog embryo. This question has not been solved and remains one of the greatest unsolved mysteries in developmental biology. Currently, a very attractive explanation attributes sequential Hox gene activation to progressive opening of the chromosome, because it parallels the linear arrangement of Hox genes on the chromosome. While promising, this explanation is surrounded by extra complexities that ensure Hox expression is synchronized between different cells. By using gain-of-function and loss-of-function approaches, I discovered that Hox-Hox interactions play a crucial role in the regulation of Hox expression, and for the first time, I dissected different roles for these interactions in axis formation. The findings are likely to resolve the above complexities, and reveal a new facet of the mechanisms underlying Hox gene regulation. Furthermore, by timed modulation of the actions of BMP signaling, I showed that there is a BMP-dependent timing mechanism in the head that could be continued by the Hox temporal sequence in the trunk. The two constitute an integrative timer which can be translated into spatial patterns of gene expression along the whole head-tail axis via a BMP/anti-BMP dependent mechanism. Show less
In this thesis, longitudinal analyses have been performed on the PROPARK-Cohort, a hospital-based cohort of 421 patients followed for a period of five years. The main focus of this thesis was... Show moreIn this thesis, longitudinal analyses have been performed on the PROPARK-Cohort, a hospital-based cohort of 421 patients followed for a period of five years. The main focus of this thesis was to determine which predictors and associated factors contributed to the development of certain non-motor symptoms in Parkinson’s disease (PD). Strengths of our cohort study include the length of the follow-up period, broad clinical characterization, limited loss-to-follow-up and the large cohort size. The following non-motor symptoms have been addressed in this thesis: psychosis (hallucinations), dementia, excessive daytime sleepiness (EDS), insomnia, depression and anxiety. We found that while certain non-motor symptoms are inherent components of PD that increase in severity as the disease progresses, others symptoms such as excessive daytime sleepiness are inarguably caused by antiparkinsonian medication. For the future, we hope to see more longitudinal data on the disease progression in PD from large cohorts. Knowledge from longitudinal studies does not only contribute to more insight in the underlying pathobiology of PD, but it could also help the caregiver to monitor patients with particular risk factors more closely and adjust treatment if necessary. Show less
